生物等效性和生物利用度杂志

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Pharmacological Efficacy of Insulin-Loaded Granules Made Up of Various Grades of Hydroxypropyl Methylcellulose in Normal Rats

Jasbir Singh, Gajendra Singh and Harmeet Kaur

The aim was to study the potential of various hydroxypropyl methylcellulose (HPMC) grades (K100LV, E50LV, E5LV, E4M, K4M and K100M) in enhancing oral bioavailability of insulin. Enteric coated insulin-loaded-HPMC granules were compared with peroral solution of zinc insulin in glycerine IP (0.788 mg/0.2 ml). Since lowering of blood glucose levels (BGLs) was used as pharmacological response, the area above curve 24 0 AAC was measured as a pharmacokinetic parameter instead of area under curve (AUC) for calculating bioavailability or pharmacological efficacy. In vitro studies showed that insulin release from granules was barred in acidic medium while almost complete release took place in basic medium upto 8h. In vivo studies in normal rats showed a maximum blood glucose reduction by K100LV based insulin-loaded granules, which corresponded to a relative pharmacological efficacy of ~1.4% and absolute pharmacological efficacy of ~0.5%. In contrast, neither control granules nor control (peroral) solution showed a comparable effect. The multiple comparison post-hoc test, least square difference (LSD; at p = 0.05), showed a significant difference of K100LV-, E50LV-, E5LV-, E4M- based insulin-loaded granules from placebo and of K100LV-, E50LV- based insulin-loaded granules from peroral solution. The potential of insulin-loaded HPMC granules followed a general order of K100LV > E50LV > E5LV > E4M > K4M > K100M in lowering of % BGLs. Therefore, low viscosity grades of HPMC are efficient in enhancing oral insulin absorption as compared to high viscosity grades.